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Importance: Cyclophosphamide and calcineurin inhibitors are the most used nonsteroid immunosuppressive medications globally for children with various chronic inflammatory conditions. Their comparative effectiveness remains uncertain, leading to worldwide practice variation. Nephrotic syndrome is the most common kidney disease managed by pediatricians globally and suboptimal treatment is associated with high morbidity., Objective: To evaluate the comparative effectiveness of cyclophosphamide vs calcineurin inhibitors (tacrolimus or cyclosporine) for childhood nephrotic syndrome relapse prevention., Design, Setting, and Participants: Using target trial emulation methods, the study team emulated a pragmatic, open-label clinical trial using available data from the Insight Into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics (INSIGHT) study. INSIGHT is a multicenter, prospective cohort study in the Greater Toronto Area, Canada. Participants included children (1 to 18 years) with steroid-sensitive nephrotic syndrome diagnosed between 1996 and 2019 from the Greater Toronto Area, who initiated cyclophosphamide or a calcineurin inhibitor treatment. Data analysis was performed in 2024., Exposures: Incident cyclophosphamide or calcineurin inhibitor treatment. Randomization was emulated by overlap weighting of propensity scores for treatment assignment., Main Outcomes: The primary outcome was time to relapse, analyzed by weighted Kaplan-Meier and Cox proportional hazards models. Secondary outcomes included relapse rates, subsequent immunosuppression, kidney function, hypertension, adverse events, and quality of life., Results: Of 578 children (median age at diagnosis, 3.7 [IQR, 2.8-6.0] years; 371 male [64%] and 207 female [36%]), 252 initiated cyclophosphamide, 131 initiated calcineurin inhibitors, and 87 sequentially initiated both medications. Baseline characteristics were well balanced after propensity score weighting. During median 5.5-year (quarter 1 to quarter 3, 2.5-9.2) follow-up, there was no significant difference in time to relapse between calcineurin inhibitor vs cyclophosphamide treatment (hazard ratio [HR], 1.25; 95% CI, 0.84-1.87). Relapses were more common after calcineurin inhibitor treatment than cyclophosphamide (85% vs 73%) in the weighted cohorts, but not statistically significant. There were also no significant differences in subsequent relapse rates, nonsteroid immunosuppression use, or kidney function between medications. Calcineurin inhibitor treatment was associated with more hospitalizations (HR, 1.83; 95% CI, 1.14-2.92) and intravenous albumin use (HR, 2.81; 95% CI, 1.65-4.81)., Conclusions and Relevance: In this study, there was no evidence of difference in time to relapse after cyclophosphamide and calcineurin inhibitor treatment in children with nephrotic syndrome. Cyclophosphamide treatment is shorter in duration and more accessible globally than calcineurin inhibitors.

Preoperative assessment of functional capacity with the six-minute walk test (6MWT) allows for estimation of surgical risk and targeted triage to prehabilitation services. Patient with abdominal and pelvic cancers have worse preoperative function compared with the general population. However, six-minute walk distance (6MWD) reference values from cancer patients are unknown, which limits the interpretation of 6MWT in this population. This study aimed to establish an explanatory reference value model for preoperative 6MWD in patients with abdominal or pelvic cancers undergoing elective surgery. Adult patients undergoing surgery for abdominal or pelvic cancers at major international hospitals were included. The 6MWT was assessed before surgery using a standardised protocol. Anthropometric data including age, sex, height, weight and body mass index (BMI) were collected and included in multiple linear regression analysis to model preoperative 6MWD. A total of 742 patients were included. Age, height and BMI were correlated with 6MWD. Six regression models were estimated, including two from the entire cohort, two from the subset of males and two from the subset of females. A sex-neutral model was the most representative, explaining 15% of the variance in 6MWD (6MWD = 761.00-3.00 * Age (years) -2.86 * BMI (kg/m 2 ) - 48.09 * Sex (M1, F2)). The explored regression models, using anthropometric variables, poorly explained the variance between measured and modelled 6MWD, which suggests that these models have no clinical utility in the cancer population. Consideration of additional, non-anthropometric variables may improve regression modelling of preoperative 6MWD in patients in abdominal and pelvic cancers., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.